Radiation-induced tumorigenesis in preneoplastic mouse mammary glands in vivo: significance of p53 status and apoptosis.

TitleRadiation-induced tumorigenesis in preneoplastic mouse mammary glands in vivo: significance of p53 status and apoptosis.
Publication TypeJournal Article
Year of Publication1998
AuthorsMedina D, Stephens LC, Bonilla PJ, Hollmann CA, Schwahn D, Kuperwasser C, Jerry DJ, Butel JS, Meyn RE
JournalMol Carcinog
Volume22
Issue3
Pagination199-207
Date Published1998 Jul
ISSN0899-1987
KeywordsAnimals, Apoptosis, Base Sequence, DNA Primers, Genes, p53, Mammary Neoplasms, Experimental, Mice, Mice, Inbred BALB C, Neoplasms, Radiation-Induced, Precancerous Conditions
Abstract

In mouse mammary tumorigenesis, p53 mutations facilitate tumorigenesis in concert with other oncogenic alterations. Ionizing radiation enhances tumorigenesis in preneoplastic mammary outgrowth lines and induces p53-dependent apoptosis. We asked if normal p53 function modulates radiation-induced tumorigenesis in preneoplastic mammary lesions by affecting the apoptotic pathway of cell deletion. Three different hyperplastic outgrowth lines were compared. Outgrowth line D1 overexpressed wild-type p53 and responded to irradiation with enhanced tumorigenicity but no induction of apoptosis. Outgrowth line TM12 exhibited normal wild-type p53 expression and responded to irradiation with no alteration in tumorigenicity but with a marked increase in apoptosis. Outgrowth line TM2L also exhibited normal wild-type p53 expression and responded to irradiation with a marked enhancement in both tumorigenicity and apoptosis. These results indicate that the two radiation-induced responses, apoptosis and tumorigenesis, are dissociable events in the mammary gland. Furthermore, radiation-induced tumorigenicity was not abrogated by either enhanced wild-type p53 expression or a robust apoptotic response. The radiation dose of 5 Gy most likely induces multiple genetic alterations in surviving cells, including genomic instability, and this may account for the tumorigenicity. Future experiments will examine lower doses of irradiation that still induce a significant apoptotic response but significantly less genomic instability.

Alternate JournalMol. Carcinog.
PubMed ID9688146